title: Vasopressin compared with norepinephrine augments the decline of plasma cytokine levels in septic shock.
abstract: BACKGROUND
  Changes in plasma cytokine levels may predict mortality, and therapies (vasopressin versus norepinephrine) could change plasma cytokine levels in early septic shock.
  
  
  OBJECTIVE
  Our hypotheses were that changes in plasma cytokine levels over 24 hours differ between survivors and nonsurvivors, and that there are different effects of vasopressin and norepinephrine on plasma cytokine levels in septic shock.
  
  
  METHODS
  We studied 394 patients in a randomized, controlled trial of vasopressin versus norepinephrine in septic shock. We used hierarchical clustering and principal components analysis of the baseline cytokine concentrations to subgroup cytokines; we then compared survivors to nonsurvivors (28 d) and compared vasopressin- versus norepinephrine-induced changes in cytokine levels over 24 hours.
  
  
  RESULTS
  A total of 39 plasma cytokines were measured at baseline and at 24 hours. Hierarchical clustering and principal components analysis grouped cytokines similarly. Survivors (versus nonsurvivors) had greater decreases of overall cytokine levels (P < 0.001). Vasopressin decreased overall 24-hour cytokine concentration compared with norepinephrine (P = 0.037). In less severe septic shock, the difference in plasma cytokine reduction over 24 hours between survivors and nonsurvivors was less pronounced than that seen in more severe septic shock. Furthermore, vasopressin decreased interferon-inducible protein 10 and granulocyte colony-stimulating factor more than did norepinephrine in less severe septic shock, whereas vasopressin decreased granulocyte-macrophage colony-stimulating factor in patients who had more severe shock.
  
  
  CONCLUSIONS
  Survivors of septic shock had greater decreases of cytokines, chemokines and growth factors in early septic shock. Vasopressin decreased 24-hour plasma cytokine levels more than did norepinephrine. The vasopressin-associated decrease of cytokines differed according to severity of shock. Clinical trial registered with www.controlled-trials.com (ISRCTN94845869).
authors.affiliation: James Hogg Research Centre, St. Paul's Hospital, University of British Columbia, Vancouver, British Columbia, Canada. jim.russell@hli.ubc.ca
authors.forename: James A
authors.initials: JA
authors.lastname: Russell
authors.forename: Chris
authors.initials: C
authors.lastname: Fjell
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Hsu
authors.forename: Terry
authors.initials: T
authors.lastname: Lee
authors.forename: John
authors.initials: J
authors.lastname: Boyd
authors.forename: Simone
authors.initials: S
authors.lastname: Thair
authors.forename: Joel
authors.initials: J
authors.lastname: Singer
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Patterson
authors.forename: Keith R
authors.initials: KR
authors.lastname: Walley
mesh_terms: D000293:Adolescent; D000316:Adrenergic alpha-Agonists / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D016207:Cytokines / Q000097:blood*; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000627:therapeutic use*; D012772:Shock, Septic / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D015996:Survival Rate / Q000639:trends; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D014662:Vasoconstrictor Agents / Q000627:therapeutic use; D014667:Vasopressins / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000316:Adrenergic alpha-Agonists; D015415:Biomarkers; D016207:Cytokines; D014662:Vasoconstrictor Agents; D014667:Vasopressins; D009638:Norepinephrine